Pharmaceutical drug moxifloxacin

The invention relates to the field of medicine and relates to a pharmaceutical preparation for oral administration containing moxifloxacin or its salt and/or hydrate, at least one dry binder. at least one auxiliary agent, contributing to the collapse of at least one lubricant and from 2.5 to 25% lactose. The drug is intended to combat bacterial infections in humans and animals and has a high hardness and good release properties. 8 C.p. f-crystals, 3 ill.

This invention relates to a pharmaceutical preparation for oral administration containing moxifloxacin, its salt and/or hydrate, as well as lactose, method of its production and its use for combating bacterial infections in humans or animals.

Moxifloxacin (INN - International nonproprietary name) is an antibiotic following formula:

1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4,3,0]non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-hinolan carboxylic acid.

This highly effective anti-infective agent, which first described in European patent application EP-A-0350733. EP-A-0350733 OPI the starch, poly(1-vinyl)-2-pyrrolidone (insoluble), highly dispersed silicon dioxide and magnesium stearate.

In European patent application EP-A-0230881 described pharmaceuticals ciprofloxacin, it is also about antibiotic from a class hinolincarbonova acids. The dosage form of ciprofloxacin corresponds to the dosage form described in EP-A-350733. In case of using famous in accordance with the prior art dosage forms for moxifloxacin can get the pill unexpectedly high hardness and mechanical strength, for example, in the manufacture of tablets blister packs, which have also improved release at a sufficiently high predetermined hardness. The authors of the present invention has set itself the task to receive pharmaceutical form for the production of tablets with a sufficient hardness and, accordingly, mechanical strength, which at the same time have excellent release property.

The inventors unexpectedly found that this problem can be solved pharmaceutical form containing lactose in a mass quantity.

The object of this invention is a pharmaceutical PR is gateline means, contributing to the collapse (disintegrator), and optionally a lubricant, with the specified product contains 2.5 to 25% lactose (all of these % are weight percentages relative to the total weight of the pharmaceutical preparation).

The object of the invention is also a method of making tablets that contain these drugs.

In accordance with the invention, in the case of a pharmaceutical product we are talking about the drug for oral administration.

Salt moxifloxacin include, for example, acid additive salts, salts of hydrochloric acid, sulfuric acid, acetic acid, lactic acid, and so forth, as well as salts with bases such as sodium hydroxide, potassium hydroxide and so forth, and/or their hydrates, such as, for example, particularly preferred in accordance with the invention moxifloxacin-hydrochloride and its monohydrate.

Described in the present invention, the form includes preferably from 50 to 85%, particularly preferably from 60 to 80%, moxifloxacin or its salt and/or hydrate.

A single dose of the pharmaceutical preparation contains mostly from 50 to 800 mg of moxifloxacin, preferably from 100 to 600 mg, particularly preferably from 200 to 400 mg

Use the manhole described in the present invention a pharmaceutical preparation, possess excellent hardness and mechanical strength and at the same time excellent release property. Another advantage of a pharmaceutical product of the present invention is that it is suitable for simple granulation, and can be used as micronized and namiranian active substance, and in both cases, you can get biosimilar pharmaceutical forms.

To solve the present invention tasks pharmaceutical preparation contains from 2.5% to 25% lactose, preferably from 5 to 20% lactose and particularly preferably from 7.5 to 16% lactose. It is preferable to use, in accordance with the invention the usual lactose monohydrate.

In accordance with the invention, the pharmaceutical preparation contains at least one dry binder selected from the group of microcrystalline cellulose, fibrous cellulose, calcium phosphate and mannitol. Particularly preferably used in accordance with the invention, microcrystalline cellulose. It is commercially available under the name Avicel® (avicel). The pharmaceutical preparation contains preferably from 5 to 30%, preferably from 6.9% to 30%, particularly preferably from 12 to 25% dry swathwidth, contributing to the collapse selected for example, from the group of starch, elastometry starch, starch glycolate, cross-linked polyvinylpyrrolidone and sodium carboxymethyl cellulose (sodium crosscarmellose). In accordance with the invention is particularly preferable to use sodium to croscarmelose. It is advisable that the pharmaceutical preparation contains from 1 to 10%, preferably from 1.5 to 8%, especially preferably from 2 to 6% auxiliary funds, contributing to the collapse.

The pharmaceutical preparation of the present invention contains at least one lubricating agent, which is selected from the group of fatty acids and their salts. In accordance with the invention is particularly preferable to use magnesium stearate. Lubricant should be used in the amount of 0.3 to 2.0%, particularly preferably from 0.4 to 1.5% and most preferably from 0.5 to 1%.

Particularly preferably, the pharmaceutical preparation of the present invention contains:

from 60 to 70% of moxifloxacin or its salt and/or hydrate

from 7.5 to 16% lactose,

from 2% to 6% sodium croscarmelose,

from 0.5 to 1.1% of magnesium stearate, and

up to 30% of microcrystalline cellulose.

Pharmaceutical drug this dry binder and lactose, then the obtained granulate is mixed with at least one auxiliary means conducive to decay, and at least one lubricating agent and, if necessary, tabletirujut and varnished.

When granulating utilize the principle of high-speed granulation. The granulation can be carried out with water without the addition of adhesive means.

The pharmaceutical preparation of the present invention is particularly preferably used in the form of pills, which can be covered with a varnish. (As mentioned above, given in the description of the application of weight refer to the total weight of the pharmaceutical drug without weight available lacquer coating). As plakiruyuschego tools can be used in common for the pharmaceutical industry varnishes, as, for example, on the basis of hydroxypropylmethylcellulose (HPMC) and/or polyethylene glycol of various molecular weights. Lakiruyuschii tool may also contain ordinary pigments, such as titanium dioxide or red iron oxide.

The pharmaceutical preparation of the present invention is preferably used for the treatment or prevention of bacterial infections in humans or animals.

Examples

Example 1

Tablets containing 50 mg moxif is itie varnish), mg:

Example 2

Tablets containing 50 mg of moxifloxacin as the active substance, the active substance of about 80% (calculated on the pill, not lacquered), mg:

Example 3

Tablets containing 50 mg of moxifloxacin as the active substance, the active substance of about 65% (calculated based tablets), mg:

Example 4

Tablet containing 200 mg of moxifloxacin in the form of micronized active substance, mg:

Example 5

Tablet containing 400 mg of moxifloxacin in the form of micronized active substance, mg:

In Fig.1 shows a comparison of the mechanical strength of the tablets according to example 6 and dosage forms according to the European patent application EP-A-0350733 (page 53).

In Fig.2 shows a comparison of the release of moxifloxacin hydrochloride tablets according to example 6 and dosage forms according to the European patent application EP-A-0350733.

All the tablets obtained in the same laboratory conditions, granulation and tabletirovanija.

Fig.1 shows clearly improved the hardness of the tablets according to the present invention. The speed of release of the active substance from the tablets of the present invention above, as shown in Fig.2.

In Fig.3 shows the curves of the level of active substance in the blood for tablets according to example 5 and example 6.

When comparing tablets in accordance with item is moxifloxacin hydrochloride) regarding their bioequivalence discovered an unexpected benefit of the pharmaceutical form according to the present invention, namely, that despite the distinctly different particle sizes of the active substance both forms have the same curves of blood. Thus, in the manufacture of pharmaceutical forms of the present invention does not require stage micronization, which can avoid the associated costs.

Claims

1. Pharmaceutical preparation for oral administration containing moxifloxacin or its salt and/or hydrate, at least one dry binder, at least one auxiliary agent, contributing to the collapse, and at least one lubricant, wherein the product contains from 2.5 to 25% lactose.

2. Pharmaceutical preparation for oral application under item 1, wherein the unit dose contains from 50 to 800 mg of moxifloxacin or its salt and/or hydrate.

3. Pharmaceutical preparation for oral application under item 1 or 2, wherein the dry binder is microcrystalline cellulose.

4. Pharmaceutical preparation for oral administration in one of the paragraphs.1-3, characterized in that the auxiliary tool, contributing to the collapse, is sodium crosscarmellose.

5. Pharmaceutical preparation for oral. Pharmaceutical preparation for oral administration in one of the paragraphs.1-5, characterized in that it contains from 60 to 76% of moxifloxacin or its salt and/or hydrate, from 7.5 to 16% lactose, 2 to 6% croscarmellose sodium, from 0.5 to 1.1% of magnesium stearate and up to 30% of microcrystalline cellulose.

7. Pharmaceutical preparation for oral administration in one of the paragraphs.1-6, characterized in that it is a tablet consisting of a core and the applied lacquer coating, the core includes the ingredients of the drug.

8. Pharmaceutical preparation for oral administration in one of the paragraphs.1-7, characterized in that it contains hydrochloride moxifloxacin.

9. Pharmaceutical preparation for oral administration according to PP.1-8 to fight bacterial infections in humans or animals.